The objective of the present proposal is to continue to examine the effects of aging on the cellular and subcellular parameters of the humoral immune response. Studies will be directed at establishing the effect of aging on the activation of both T and B cells and the ability of macrophages to present antigen in this interaction. Special attention will be given to the effect of aging on the ability of these two cells to communicate with the help of macrophages. The effect of aging on the ability of T cells to be activated, as detected by the proliferative response and the ability of these cells to release effective lymphokines, will be approached using a model of lymphocyte activation involving stimulation by subfragments of the Fc portion of immunoglobulin. Other studies will be carried out to determine the effect of aging on the activation of B cells to proliferate and the ability of these proliferating B cells to receive and act upon signals given by T cell lymphokines. The ability of both B and T cells to receive effective signals from macrophages will also be investigated as will the effect of aging on the ability of macrophages to generate effective signals and present antigen to the T cell. A comparison of these immunological events will be made in mice at various ages during life. Studies will be carried out in both long-lived strains of mice and those that are short-lived. Other studies will attempt to clarify the cellular events that are involved in both the regulation of the immune response by Fc subfragments and the change of such regulation during the aging process. The effect of aging on the cellular and subcellular events involved in the induction of tolerance in both T and B lymphocytes will also be approached in an attempt to better understand the change in self-nonself recognition during the aging process. The results of these experiments will be used to address the effect of aging on the induction of experimental autoimmune diseases.